Gelatin methacryloyl hydrogel as an injectable scaffold with multi-therapeutic effects to promote antimicrobial disinfection and angiogenesis for regenerative endodontics.

Regenerative endodontics represents a paradigm shift in dental pulp therapy for necrotic young permanent teeth. However, there are still challenges associated with attaining maximum root canal disinfection while supporting angiogenesis and preserving resident stem cells viability and differentiation capacity. Here, we developed a hydrogel system by incorporating antibiotic-eluting fiber-based microparticles in gelatin methacryloyl (GelMA) hydrogel to gather antimicrobial and angiogenic properties while prompting minimum cell toxicity. Minocycline (MINO) or clindamycin (CLIN) was introduced into a polymer solution and electrospun into fibers, which were further cryomilled to attain MINO- or CLIN-eluting fibrous microparticles. To obtain hydrogels with multi-therapeutic effects, MINO- or CLIN-eluting microparticles were suspended in GelMA at distinct concentrations. The engineered hydrogels demonstrated antibiotic-dependent swelling and degradability while inhibiting bacterial growth with minimum toxicity in dental-derived stem cells. Notably, compared to MINO, CLIN hydrogels enhanced the formation of capillary-like networks of endothelial cells in vitro and the presence of widespread vascularization with functioning blood vessels in vivo. Our data shed new light onto the clinical potential of antibiotic-eluting gelatin methacryloyl hydrogel as an injectable scaffold with multi-therapeutic effects to promote antimicrobial disinfection and angiogenesis for regenerative endodontics.

Synthesis and characterization of calcium-releasing elastomeric resin-based endodontic sealers.

OBJECTIVES: To evaluate the incorporation of halloysite nanotubes (HNTs) loaded with one of two calcium sources (i.e., calcium hydroxide/CaOH2 or beta-tricalcium phosphate/ß-TCP) on the physicochemical and biological properties of an experimental resin-based dual-cured endodontic sealer. MATERIALS AND METHODS: HNTs were encapsulated with CaOH2 or ß-TCP at 10 wt.%. HNTs containing CaOH2 or ß-TCP were added into the experimental sealers at 50 wt.%. The control sealers were the calcium-free HNT-modified resin-based experimental sealer and AH Plus™, a commercially available endodontic sealer. Degree of conversion, setting time, flow, film thickness, radiopacity, dimensional stability, and calcium ions release were determined. Antibiofilm properties and cytocompatibility of the formulated sealers and commercial control were also evaluated. One and two-way ANOVA analysis followed by Tukey's post hoc test was conducted to evaluate the effect of the independent variable on the evaluated properties. RESULTS: FTIR confirmed the encapsulation of calcium sources into HNTs. Regarding flow and film thickness, the values obtained from these sealers were in accordance with the specifications provided by ISO 6876. For radiopacity, AH Plus™ achieved the highest radiopacity (p<0.05). Among the experimental formulations, all experimental HNT-containing compositions exhibited values below 3 mm Al. The experimental sealers showed greater dimensional changes when compared to the commercial (AH Plus™) control. The release of calcium ions was observed for the HNT_CaOH2 and HNT_ß-TCP sealers without statistical differences. Experimental sealers containing HNT_CaOH2 and HNT_ß-TCP significantly reduced the CFU/mL count and showed cell compatibility. CONCLUSIONS: The findings of this study demonstrate that the incorporation of HNT_CaOH2 or HNT_ß-TCP into resin-based experimental sealers promoted antimicrobial effects and gradual calcium release without impairing cytocompatibility or physicochemical properties of the sealers. Still, an adjustment to reach the minimal radiopacity established by ISO 6876 is needed. CLINICAL RELEVANCE: The experimental resin-based sealers seemed to be an alternative for endodontics. The incorporation of calcium sources exerts promising antimicrobial effects while displaying low cell toxicity.

Natural monoterpenes-laden electrospun fibrous scaffolds for endodontic infection eradication.

This investigation aimed to synthesize poly(D,L-lactide) (PLA)-based fibrous scaffolds containing natural essential oils (i.e., linalool and citral) and determine their antimicrobial properties and cytocompatibility as a clinically viable cell-friendly disinfection strategy for regenerative endodontics. PLA-based fibrous scaffolds were fabricated via electrospinning with different concentrations of linalool and citral. The micromorphology and average diameter of the fibers was investigated through scanning electron microscopy (SEM). The chemical composition of the scaffolds was inferred by Fourier-transform infrared spectroscopy (FTIR). Antimicrobial efficacy against Enterococcus faecalis and Actinomyces naeslundii was also evaluated by agar diffusion and colony-forming units (CFU) assays. The scaffolds' cytocompatibility was determined using dental pulp stem cells (DPSCs). Statistical analyses were performed and the significance level was set at α = 5%. Linalool and citral's incorporation in the PLA fibrous scaffolds was confirmed in the FTIR spectra. SEM images indicate no morphological changes upon inclusion of the essential oils, except the reduced diameter of 40% linalool-laden fibers (p < 0.05). Importantly, significant antimicrobial properties were reported for citral-containing scaffolds for CFU/mL counts (p < 0.05), while only 20% and 40% linalool-laden scaffolds reduced CFU/mL (p < 0.05). Meanwhile, the inhibition halos were verified in a concentration-dependent manner for all monoterpenes-laden scaffolds. Citral- and linalool-laden PLA-based fibrous scaffolds showed acceptable cytocompatibility. The incorporation of natural monoterpenes did not alter the scaffolds' fibrous morphology, promoted antimicrobial action against endodontic pathogens, and preserved DPSCs viability. Linalool- and citral-laden electrospun scaffolds hold promise as naturally derived antimicrobial therapeutics for applications in regenerative endodontics.

Electrospun Azithromycin-Laden Gelatin Methacryloyl Fibers for Endodontic Infection Control.

This study was aimed at engineering photocrosslinkable azithromycin (AZ)-laden gelatin methacryloyl fibers via electrospinning to serve as a localized and biodegradable drug delivery system for endodontic infection control. AZ at three distinct amounts was mixed with solubilized gelatin methacryloyl and the photoinitiator to obtain the following fibers: GelMA+5%AZ, GelMA+10%AZ, and GelMA+15%AZ. Fiber morphology, diameter, AZ incorporation, mechanical properties, degradation profile, and antimicrobial action against Aggregatibacter actinomycetemcomitans and Actinomyces naeslundii were also studied. In vitro compatibility with human-derived dental pulp stem cells and inflammatory response in vivo using a subcutaneous rat model were also determined. A bead-free fibrous microstructure with interconnected pores was observed for all groups. GelMA and GelMA+10%AZ had the highest fiber diameter means. The tensile strength of the GelMA-based fibers was reduced upon AZ addition. A similar pattern was observed for the degradation profile in vitro. GelMA+15%AZ fibers led to the highest bacterial inhibition. The presence of AZ, regardless of the concentration, did not pose significant toxicity. In vivo findings indicated higher blood vessel formation, mild inflammation, and mature and thick well-oriented collagen fibers interweaving with the engineered fibers. Altogether, AZ-laden photocrosslinkable GelMA fibers had adequate mechanical and degradation properties, with 15%AZ displaying significant antimicrobial activity without compromising biocompatibility.

Self-assembling peptide-laden electrospun scaffolds for guided mineralized tissue regeneration.

OBJECTIVES: Electrospun scaffolds are a versatile biomaterial platform to mimic fibrillar structure of native tissues extracellular matrix, and facilitate the incorporation of biomolecules for regenerative therapies. Self-assembling peptide P11-4 has emerged as a promising strategy to induce mineralization; however, P11-4 application has been mostly addressed for early caries lesions repair on dental enamel. Here, to investigate P11-4's efficacy on bone regeneration, polymeric electrospun scaffolds were developed, and then distinct concentrations of P11-4 were physically adsorbed on the scaffolds. METHODS: P11-4-laden and pristine (P11-4-free) electrospun scaffolds were immersed in simulated body fluid and mineral precipitation identified by SEM. Functional groups and crystalline phases were analyzed by FTIR and XRD, respectively. Cytocompatibility, mineralization, and gene expression assays were conducted using stem cells from human exfoliated deciduous teeth. To investigate P11-4-laden scaffolds potential to induce in vivo mineralization, an established rat calvaria critical-size defect model was used. RESULTS: We successfully synthesized nanofibrous (∼ 500 nm fiber diameter) scaffolds and observed that functionalization with P11-4 did not affect the fibers' diameter. SEM images indicated mineral precipitation, while FTIR and XRD confirmed apatite-like formation and crystallization for P11-4-laden scaffolds. In addition, P11-4-laden scaffolds were cytocompatible, highly stimulated cell-mediated mineral deposition, and upregulated the expression of mineralization-related genes compared to pristine scaffolds. P11-4-laden scaffolds led to enhanced in vivo bone regeneration after 8 weeks compared to pristine PCL. SIGNIFICANCE: Electrospun scaffolds functionalized with P11-4 are a promising strategy for inducing mineralized tissues regeneration in the craniomaxillofacial complex.

Photocrosslinkable methacrylated gelatin hydrogel as a cell-friendly injectable delivery system for chlorhexidine in regenerative endodontics.

OBJECTIVES: This work sought to formulate photocrosslinkable chlorhexidine (CHX)-laden methacrylated gelatin (CHX/GelMA) hydrogels with broad spectrum of action against endodontic pathogens as a clinically viable cell-friendly disinfection therapy prior to regenerative endodontics procedures. METHODS: CHX/GelMA hydrogel formulations were successfully synthesized using CHX concentrations between 0.12 % and 5 % w/v. Hydrogel microstructure was evaluated by scanning electron microscopy (SEM). Swelling and enzymatic degradation were assessed to determine microenvironmental effects. Compression test was performed to investigate the influence of CHX incorporation on the hydrogels' biomechanics. The antimicrobial and anti-biofilm potential of the formulated hydrogels were assessed using agar diffusion assays and a microcosms biofilm model, respectively. The cytocompatibility was evaluated by exposing stem cells from human exfoliated deciduous teeth (SHEDs) to hydrogel extracts (i.e., leachable byproducts obtained from overtime hydrogel incubation in phosphate buffer saline). The data were analyzed using One- and Two-way ANOVA and Tukey's test (α = 0.05). RESULTS: CHX/GelMA hydrogels were effectively prepared. NMR spectroscopy confirmed the incorporation of CHX into GelMA. The addition of CHX did not change the micromorphology (pore size) nor the swelling profile (p > 0.05). CHX incorporation reduced the degradation rate of the hydrogels (p < 0.001); whereas, it contributed to increased compressive modulus (p < 0.05). Regarding the antimicrobial properties, the incorporation of CHX showed a statistically significant decrease in the number of bacteria colonies at 0.12 % and 0.5 % concentration (p < 0.001) and completely inhibited the growth of biofilm at concentration levels 1 %, 2 %, and 5 %. Meanwhile, the addition of CHX, regardless of the concentration, did not lead to cell toxicity, as cell viability values were above 70 %. SIGNIFICANCE: The addition of CHX into GelMA showed significant antimicrobial action against the pathogens tested, even at low concentrations, with the potential to be used as a cell-friendly injectable drug delivery system for root canal disinfection prior to regenerative endodontics.

Effect of Different Numbers of Interset Antagonist Proprioceptive Neuromuscular Facilitation Stretching on the Total Number of Repetitions for the Agonists.

Recent studies have observed that stretching applied to antagonist muscles can promote improvement in agonist muscle performance. The purpose of this study was to investigate the effect of different numbers of interset proprioceptive neuromuscular facilitation (PNF) stretching for the antagonists on the total number of repetitions completed for the agonists (quadriceps) in the leg extension exercise. Fourteen physically active individuals (age: 29.35 ± 10.5 years; body mass: 79.1 ± 11.34 kg; height: 170.4 ± 8.7 cm) participated in this study. The following experimental protocols were performed: 1) Traditional protocol (Traditional) - without previous stretching; 2) PNF with lesser duration (PNF1-3 sets of 20 secs.); 3) PNF with greater duration (PNF2-3 sets of 30 secs.). Within the experimental protocols (PNF1 and PNF2), stretching exercises for the antagonists were performed before and between the four sets of the unilateral leg extension exercise. All tests were performed on the dominant limb only. The results showed that there was a significant difference in the total number of repetitions for the PNF2 protocol versus the Traditional protocol (p = 0.026). However, there was no significant difference between the PNF1 protocol versus the Traditional protocol (p = 0.577). In conclusion, in the leg extension exercise, an extended duration of interset PNF stretching for the hamstrings, promoted greater contractile performance for the quadriceps as demonstrated by significantly greater total repetitions over four sets.

Engineering of Injectable Antibiotic-laden Fibrous Microparticles Gelatin Methacryloyl Hydrogel for Endodontic Infection Ablation.

This study aimed at engineering cytocompatible and injectable antibiotic-laden fibrous microparticles gelatin methacryloyl (GelMA) hydrogels for endodontic infection ablation. Clindamycin (CLIN) or metronidazole (MET) was added to a polymer solution and electrospun into fibrous mats, which were processed via cryomilling to obtain CLIN- or MET-laden fibrous microparticles. Then, GelMA was modified with CLIN- or MET-laden microparticles or by using equal amounts of each set of fibrous microparticles. Morphological characterization of electrospun fibers and cryomilled particles was performed via scanning electron microscopy (SEM). The experimental hydrogels were further examined for swelling, degradation, and toxicity to dental stem cells, as well as antimicrobial action against endodontic pathogens (agar diffusion) and biofilm inhibition, evaluated both quantitatively (CFU/mL) and qualitatively via confocal laser scanning microscopy (CLSM) and SEM. Data were analyzed using ANOVA and Tukey's test (α = 0.05). The modification of GelMA with antibiotic-laden fibrous microparticles increased the hydrogel swelling ratio and degradation rate. Cell viability was slightly reduced, although without any significant toxicity (cell viability > 50%). All hydrogels containing antibiotic-laden fibrous microparticles displayed antibiofilm effects, with the dentin substrate showing nearly complete elimination of viable bacteria. Altogether, our findings suggest that the engineered injectable antibiotic-laden fibrous microparticles hydrogels hold clinical prospects for endodontic infection ablation.

Metformin-loaded nanospheres-laden photocrosslinkable gelatin hydrogel for bone tissue engineering.

The aim of this investigation was to engineer metformin (MF)-loaded mesoporous silica nanospheres (MSNs)-laden gelatin methacryloyl (GelMA) photocrosslinkable hydrogels and test their effects on the mechanical properties, swelling ratio, drug release, cytocompatibility, and osteogenic differentiation of stem cells from human exfoliated deciduous teeth (SHEDs). As-received and carboxylated MSNs (MSNs-COOH) were characterized by scanning and transmission electron microscopies (SEM and TEM), as well as Fourier-transform infrared spectroscopy (FTIR) prior to hydrogel modification. MF-MSNs-COOH were obtained by loading MF into MSNs at a 1:1 mass ratio. Upon MSNs-COOH laden-hydrogels fabrication, the mechanical properties, swelling ratio and MF release were evaluated. SHEDs were seeded on the hydrogels and cytocompatibility was examined. The effects of the MF-MSNs-COOH/GelMA on the osteogenic differentiation of SHEDs were measured by ALP activity, Alizarin Red assay, and Real-time PCR. Statistics were performed using one-way ANOVA (α = 0.05). Morphological (SEM and TEM) analyses of pristine and carboxylated MSNs revealed a mean particle size of 200 nm and 218 nm, respectively. Importantly, an intrinsic nanoporous structure was noticed. Incorporation of MSNs-COOH at 1.5 mg/mL in GelMA led to the highest compressive modulus and swelling ratio. The addition of MSNs-COOH (up to 3 mg/mL) in GelMA did not impact cell viability. The presence of MF in MSNs-COOH/GelMA significantly promoted cell proliferation. Significant upregulation of osteogenic-related genes (except OCN) were seen for modified (MSNs-COOH and MF-MSNs-COOH) hydrogels when compared to GelMA. Altogether, the engineered MF-MSNs-COOH/GelMA shows great promise in craniomaxillofacial applications as an injectable, cell-free and bioactive therapeutics for bone regeneration.

Physicomechanical, optical, and antifungal properties of polymethyl methacrylate modified with metal methacrylate monomers.

STATEMENT OF PROBLEM: The high recurrence rates of denture stomatitis may be associated with the resistance of biofilms to therapeutics. Therefore, methods that provide biomaterials with antifungal properties are an attractive solution to improving microbial control. PURPOSE: The purpose of this in vitro study was to modify conventional polymethyl methacrylate (PMMA) through the incorporation of metal methacrylate monomers and to evaluate the physicomechanical and optical properties and antifungal activity of the modified materials. MATERIAL AND METHODS: Experimental denture base acrylic resins were fabricated through the addition of zirconium methacrylate (ZM), tin methacrylate (TM), and di-n-butyldimethacrylate-tin (DNBMT) to the liquid of a commercially available denture base PMMA resin. Unmodified PMMA resin was used as the control. The degree of conversion of the materials was tested through Fourier transform infrared spectroscopy (n=3). A digital spectrophotometer was used to assess the color change of the modified materials (n=8). Differences in Knoop hardness and roughness between experimental groups were also evaluated (n=8). A biofilm accumulation test with Candida albicans (ATCC 62342) (n=4) was performed for 5 days in Sabouraud broth culture supplemented with 10% sucrose. Data were subjected to analysis of variance and the post hoc Tukey honestly significant difference test (α=.05). RESULTS: The degree of conversion and color-change values of the experimental materials were statistically similar to those of the control (P=.593). The incorporation of DNBMT significantly increased the hardness of the modified material (P=.014). The ZM, TM, and DNBMT groups had higher antifungal activity against C. albicans (P=.001) and lower roughness than the control group (control 0.65 ±0.05 µm; ZM 0.34 ±0.09 µm, TM 0.34 ±0.11 µm, and DNBMT 0.41 ±0.08 µm). CONCLUSIONS: The metal-containing methacrylate monomers provided antifungal action to the modified materials without affecting the physicomechanical or optical properties of the denture base resin. ZM, TM, and DNBMT are potential reactive agents for the fabrication of PMMA denture base resins with antifungal properties.

The role of nanohydroxyapatite on the morphological, physical, and biological properties of chitosan nanofibers.

OBJECTIVES: This study aimed to evaluate the effects of nanohydroxyapatite (nHAp) particles on the morphological, chemical, physical, and biological properties of chitosan electrospun nanofibers. MATERIALS AND METHODS: nHAp particles with a 1.67 Ca/P ratio were synthesized via the aqueous precipitation method, incorporated into chitosan polymer solution (0.5 wt%), and electrospun into nHAp-loaded fibers (ChHa fibers). Neat chitosan fibers (nHAp-free, Ch fibers) were used as the control. The electrospun fiber mats were characterized using morphological, topographical, chemical, thermal, and a range of biological (antibacterial, antibiofilm, cell viability, and alkaline phosphatase [ALP] activity) analyses. Data were analyzed using ANOVA and Tukey's test (α = 0.05). RESULTS: ChHa fibers demonstrated a bead-like morphology, with thinner (331 ± 110 nm) and smoother (Ra = 2.9 ± 0.3 µm) distribution as compared to the control fibers. Despite showing similar cell viability and ALP activity to Ch fibers, the ChHa fibers demonstrated greater antibacterial potential against most tested bacteria (except for P. intermedia), and higher antibiofilm activity against P. gingivalis biofilm. CONCLUSIONS: The incorporation of nHAp particles did not jeopardize the overall morphology, topography, physical, and biological characteristics of the chitosan nanofibers. CLINICAL RELEVANCE: The combination of nHAp particles with chitosan can be used to engineer bioactive, electrospun composite nanofibers with potential applications in regenerative dentistry.

Injectable Multifunctional Drug Delivery System for Hard Tissue Regeneration under Inflammatory Microenvironments.

Engineering multifunctional hydrogel systems capable of amplifying the regenerative capacity of endogenous progenitor cells via localized presentation of therapeutics under tissue inflammation is central to the translation of effective strategies for hard tissue regeneration. Here, we loaded dexamethasone (DEX), a pleotropic drug with anti-inflammatory and mineralizing abilities, into aluminosilicate clay nanotubes (halloysite clay nanotubes (HNTs)) to engineer an injectable multifunctional drug delivery system based on photo-cross-linkable gelatin methacryloyl (GelMA) hydrogel. In detail, a series of hydrogels based on GelMA formulations containing distinct amounts of DEX-loaded nanotubes was analyzed for physicochemical and mechanical properties and kinetics of DEX release as well as compatibility with mesenchymal stem cells from human exfoliated deciduous teeth (SHEDs). The anti-inflammatory response and mineralization potential of the engineered hydrogels were determined in vitro and in vivo. DEX conjugation with HNTs was confirmed by FTIR analysis. The incorporation of DEX-loaded nanotubes enhanced the mechanical strength of GelMA with no effect on its degradation and swelling ratio. Scanning electron microscopy (SEM) images demonstrated the porous architecture of GelMA, which was not significantly altered by DEX-loaded nanotubes' (HNTs/DEX) incorporation. All GelMA formulations showed cytocompatibility with SHEDs (p < 0.05) regardless of the presence of HNTs or HNTs/DEX. However, the highest osteogenic cell differentiation was noticed with the addition of HNT/DEX 10% in GelMA formulations (p < 0.01). The controlled release of DEX over 7 days restored the expression of alkaline phosphatase and mineralization (p < 0.0001) in lipopolysaccharide (LPS)-stimulated SHEDs in vitro. Importantly, in vivo data revealed that DEX-loaded nanotube-modified GelMA (5.0% HNT/DEX 10%) led to enhanced bone formation after 6 weeks (p < 0.0001) compared to DEX-free formulations with a minimum localized inflammatory response after 7 days. Altogether, our findings show that the engineered DEX-loaded nanotube-modified hydrogel may possess great potential to trigger in situ mineralized tissue regeneration under inflammatory conditions.

Development and properties of endodontic resin sealers with natural oils.

OBJECTIVES: To synthesize and evaluate the physicochemical, antimicrobial, and cytocompatibility properties of experimental resin-based endodontic sealers containing butia or copaiba natural oils. METHODS: Experimental groups contained butia (Butia capitata) at 0.5 % (B0.5), 1 % (B1), 2 % (B2), and copaiba (Copaifera spp.) at 0.5 % (C0.5), 1 % (C1), and 2 % (C2). The control group contained no added oils (experimental material, EM) and the commercial group was a methacrylate-based resin material (RealSeal™, SybronEndo Corporation, Orange, CA, USA). Degree of conversion, film thickness, setting time, flow, water sorption and solubility, and radiopacity were measured. Meanwhile, antimicrobial (modified direct contact test) and cytotoxicity assays of the experimental groups and controls were performed. One-way ANOVA was used to determine the effect of the independent variable (material) on the degree of conversion, film thickness, radiopacity, flow, setting time, water sorption and solubility, and cytotoxicity. For antimicrobial assays, data were analyzed using two-way ANOVA and Sidák's test. RESULTS: The experimental groups containing natural oils showed higher values of degree of conversion, and lowest water sorption and solubility. EM, B0.5, B1, B2, and RS showed similar film thicknesses. The flow values were statistically similar in all groups. The experimental groups showed adequate cell compatibility. Copaiba oil at 2% increased the antimicrobial effect after 1 and 24 h (p < 0.05). The incorporation of butia or copaiba resulted in a slight modification in some physicochemical properties of the experimental resin sealers. CONCLUSION: Novel resin sealers containing natural oils are a promising alternative for endodontics, because of their good physicochemical properties, antimicrobial effects, and cytocompatibility when compared to a commercially available sealer. CLINICAL SIGNIFICANCE: Endodontic sealers containing butia or copaiba had satisfactory cytocompatibility, antimicrobial effects, and adequate physicochemical properties.

Antimicrobial Therapeutics in Regenerative Endodontics: A Scoping Review.

INTRODUCTION: This review aimed to provide a critical appraisal of alternative antimicrobial strategies in lieu of traditional triple antibiotic paste (TAP). METHODS: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The literature search was performed in 8 databases (PubMed/Medline, Embase, LILACS, Web of Science, Scopus, BVS, SciELO, and the Cochrane Library), selecting clinical, in vitro, in vivo, and in situ studies that evaluated antimicrobial alternatives to TAP in regenerative endodontics. Studies lacking an experimental TAP group were excluded. RESULTS: A total of 1705 potentially relevant records were initially identified. From the 38 studies retrieved for full-text reading, 16 fulfilled all selection criteria and were included in the qualitative analysis. According to the study design, 11 studies were solely in vitro, 1 study was both in vitro and in vivo (animal model), 2 studies were solely animal experiments, and 2 studies were clinical trials. The alternative antimicrobial agents to TAP consisted of modified TAP formulations (eg, a combination of TAP with chitosan); TAP-eluting nanofibers; propolis; chlorhexidine (CHX) gels/solutions; double antibiotic pastes composed of distinct combinations of antibiotics; Ca(OH)2-based formulations; and sodium hypochlorite. Overall, most of the alternative agents performed similarly to TAP, although some strategies (eg, Ca(OH)2- and CHX-based formulations) seemed to present dubious importance in the control of infection. CONCLUSIONS: TAP still remains an excellent option in terms of the complete elimination of microorganisms. This review points to the use of electrospun fibers as a drug delivery system to offer a controlled release of the antimicrobial agent, as well as the use of natural compounds, deserving future investigation.

Hybrid Antimicrobial Hydrogel as Injectable Therapeutics for Oral Infection Ablation.

Oral bacterial infection represents the leading cause of the gradual destruction of tooth and periodontal structures anchoring the teeth. Lately, injectable hydrogels have gained increased attention as a promising minimally invasive platform for localized delivery of personalized therapeutics. Here, an injectable and photocrosslinkable gelatin methacryloyl (GelMA) hydrogel is successfully engineered with ciprofloxacin (CIP)-eluting short nanofibers for oral infection ablation. For this purpose, CIP or its ß-cyclodextrin (ß-CD)-inclusion complex (CIP/ß-CD-IC) has been incorporated into polymeric electrospun fibers, which were subsequently cut into short nanofibers, and then embedded in GelMA to obtain an injectable hybrid antimicrobial hydrogel. Thanks to the solubility enhancement of CIP by ß-CD-IC and the tunable degradation profile of GelMA, the hydrogels promote localized, sustained, and yet effective cell-friendly antibiotic doses, as measured by a series of bacterial assays that demonstrated efficacy in attenuating the growth of Gram-positive Enterococcus faecalis. Altogether, we foresee significant potential in translating this innovative hybrid hydrogel as an injectable platform technology that may have broad applications in oral infection ablation, such as periodontal disease and pulpal pathology.

Injectable MMP-Responsive Nanotube-Modified Gelatin Hydrogel for Dental Infection Ablation.

A photocrosslinkable gelatin methacryloyl (GelMA) hydrogel has been widely examined in regenerative engineering because of its good cell-tissue affinity and degradability in the presence of matrix metalloproteinases. A halloysite aluminosilicate nanotube (HNT) is a known reservoir for the loading and sustained delivery of therapeutics. Here, we formulate injectable chlorhexidine (CHX)-loaded nanotube-modified GelMA hydrogel that is cytocompatible and biodegradable and provides sustained release of CHX for infection ablation while displaying good biocompatibility. The effects of HNTs and CHX on hydrogel degradability and mechanical properties, as well as on the kinetics of CHX release, and on the antimicrobial efficacy against oral pathogens were systematically assessed. Cytocompatibility in stem cells from human exfoliated deciduous teeth and inflammatory response in vivo using a subcutaneous rat model were determined. Our hydrogel system, that is, (CHX)-loaded nanotube-modified GelMA showed minimum localized inflammatory responses, supporting its ability for drug delivery applications. Moreover, we showed that the incorporation of CHX-loaded nanotubes reduces the mechanical properties, increases the swelling ratio, and diminishes the degradation rate of the hydrogels. Importantly, the presence of CHX-loaded nanotubes inhibits bacterial growth with minimal cell toxicity. Our findings provide a new strategy to modify GelMA hydrogel with chlorhexidine-loaded nanotubes for clinical use as an injectable drug delivery strategy for dental infection ablation.

Fabrication of electrospun poly(lactic acid) nanoporous membrane loaded with niobium pentoxide nanoparticles as a potential scaffold for biomaterial applications.

Tissue engineering aims to regenerate and restore damaged human organs and tissues using scaffolds that can mimic the native tissues. The requirement for modern and efficient biomaterials that are capable of accelerating the healing process has been considerably increased. In this work, a novel electrospun poly(lactic acid) (PLA) nanoporous membrane incorporated with niobium pentoxide nanoparticles (Nb2 O5 ) for biomaterial applications was developed. Nb2 O5 nanoparticles were obtained by microwave-assisted hydrothermal synthesis, and different concentrations (0, 1, 3, and 5% wt/wt) were tested. Chemical, morphological, mechanical, and biological properties of membranes were evaluated. Cell viability results demonstrated that the membranes presented nontoxic effects. The incorporation of Nb2 O5 improved cell proliferation without impairing the wettability, porosity, and mechanical properties of membranes. Membranes containing Nb2 O5 nanoparticles presented biocompatible properties with suitable porosity, which facilitated cell attachment and proliferation while allowing diffusion of oxygen and nutrients. This study has demonstrated that Nb2 O5 nanoparticle-loaded electrospun PLA nanoporous membranes are potential candidates for drug delivery and wound dressing applications.

Cellulose Nanocrystal Membranes as Excipients for Drug Delivery Systems.

In this work, cellulose nanocrystals (CNCs) were obtained from flax fibers by an acid hydrolysis assisted by sonochemistry in order to reduce reaction times. The cavitation inducted during hydrolysis resulted in CNC with uniform shapes, and thus further pretreatments into the cellulose are not required. The obtained CNC exhibited a homogeneous morphology and high crystallinity, as well as typical values for surface charge. Additionally, CNC membranes were developed from CNC solution to evaluation as a drug delivery system by the incorporation of a model drug. The drug delivery studies were carried out using chlorhexidine (CHX) as a drug and the antimicrobial efficiency of the CNC membrane loaded with CHX was examined against Gram-positive bacteria Staphylococcus aureus (S. Aureus). The release of CHX from the CNC membranes is determined by UV-Vis. The obtaining methodology of the membranes proved to be simple, and these early studies showed a potential use in antibiotic drug delivery systems due to the release kinetics and the satisfactory antimicrobial activity.